CANCER 1 - Using models

Question 1

How does a RETROVIRUS work?

Answer 1

Retroviruses exist as RNA and then hijack a cells replication machinery to make a copy of itself and integrates into the host DNA

Question 2

How are retroviruses linked to cancer?

Answer 2

When particular viruses integrate next to proto-oncogene promoters this can upregulate its expression and create an ONCOGENE

Question 3

What is Int1 and why was it identified as a cancerous gene?

Answer 3

Was seen to be upregulated in oncogenes –> Homologue of Wnt signalling

Question 4

Wnt – how can you tell in cells that Wnt is active? How is it mediated ?

Answer 4

Mediated by B-catenin - can tell that Wnt signalling is active when there is B catenin present in the Nucleus of the cell

Question 5

What are Wnt target genes and what do they do?

Answer 5

Cmyc/CyclinD1 —- both are cell cycle regulators

Question 6

What was shown in mice with high levels of Wnt signalling?

Answer 6

Enhanced cell proliferation which lead to tumours

Question 7

What is epistasis and how can it be helpful in the treatment of cancer?

Answer 7

Deducing the order of genes in a signalling pathway — allow us to know whether an ACTIVATOR or TUMOUR SUPRESSOR gene has been mutated

Question 8

What is APC and how is it relevant to cancer

Answer 8

Tumour supressor gene - when mutated (BOTH COPIES) Could be leading to some forms of cancer?

Question 9

What is metastasis?

Answer 9

2ndary malignant tumour formation which occurs from the primary cancer site

Question 10

How is cancer classed as a multi-stage disease?

Answer 10

Mutations accumulate over the years in cancer that give rise from adenomas to FULL BLOWN TUMOURS –> 2 hits are required for each allele normally

Question 11

Reporter cell lines and Wnt responsive cells?

Answer 11

Reporter lines could be used to see how cells respond to Wnt activation –> could see which cells are cancerous?

Question 12

What could the presence of Wnt responsive cells mean?

Answer 12

These particular stem cells proliferate in response to Wnt – Wnt promotes stem cell renewal

Question 13

What was shown about Wnt in relation to stem cells

Answer 13

Wnt was shown to cause stem cells to proliferate — Wnt promotes stem cell renewal?

Question 14

How is the intestine a good model for relation between stem cells and some cancers?
What have B catenin levels in gut crypts shown in relation to Wnt signalling?

Answer 14

Population of stem cells at the distal end of gut crypts.

INCREASED B CATENIN LEVELS in gut crypts seen in ADENOMAS (early tumour)

Question 15

How does increased Wnt signalling lead to increased cell proliferation?

Answer 15

Increased active wnt –> Increased active Rac1 –> Activation of Ras pathway –>hyperproliferation of cells

Question 16

What is NFKB and how is it related to cancers?

Answer 16

Pro-inflammatory factor which regulated the amount of cytokines and chemokines.

Question 17

Why could targeting oestrogen signalling be a cure for cancer?

What problems have been encountered in the past?

Answer 17

Oestrogen promotes cell proliferation. Targeting oestrogen signalling may therefore be a potential treatment
BCSCs have been seen to be resistant to anti-oestrogen signalling so a combination of anti-oe and anti-Wnt could be a potential breast cancer treatment?

Question 18

Why has it been difficult to prove that UPREG of WNT ALONE causes cancer?

Answer 18

Upreg of Wnt is thought to cause Adenomas (but not full blown malignant tumours) —> another further event such as high levels of inflammation is thought to cause full blown cancers

Question 19

OVERALL MECHANISM OF TUMOUR FORMATION

Answer 19

1) Tumour grows, causing the nutrient demand to outstrip the supply
2) This leads cancer cells to secrete inflammatory signals
3) Macrophages invade to break down dead cells and debris, causing the release of more CYTOKINES
4) Angiogenesis begins and the ECM breaks down

Question 20

What will be the next step in finding cancer treatments?

Answer 20

Look for interacting genes that accellerate or retard cancers and the development of tumours